T-CELL RECOGNITION OF PENICILLIN-G - STRUCTURAL FEATURES DETERMINING ANTIGENIC SPECIFICITY

Penicillin G (Pen G) and other beta-lactam antibiotics frequently indu ce allergic reactions constituting typical examples of human immune re sponses to haptens. In fact, penicillins represent a unique set of hap tens with outstanding structural variability on the basis of an identi cal protein-reactive beta-lactam containing backbone. Although both ce llular and humoral responses are involved in drug-induced allergies, l ittle is known about the T cell reactivity to penicillins. To understa nd which structural features determine antigenic specificity, we isola ted a panel of MHC-restricted, Pen G-reactive T cell clones from diffe rent penicillin-allergic patients and tested them for their capacity t o proliferate in the presence of other penicillin derivatives. We foun d that the antigenic epitope consists of both the amide-linked side ch ain, which is different in every member of the penicillin family, as w ell as the thiazolidine ring common to all penicillin derivatives. We also demonstrated the presence of two different types of penicillin-sp ecific T cells, one dependent, and the other independent of antigen pr ocessing by autologous antigen-presenting cells. Our data strongly sug gest that penicillins form part of the epitopes contacting the antigen receptors of T cells.